NMR analyzer

ABSTRACT

A first room-temperature space is formed penetrating through a cryostat along a center axis of a split-type multi-layer cylindrical superconducting coil system which has a ratio of the maximum empirical magnetic field to the central magnetic filed of not larger than 1.3 and is horizontally arranged such that the center axis of the coil is in the horizontal direction, a room-temperature shim coil system is arranged in said first room-temperature space to improve the homogeneity of the magnetic field, a second room-temperature space is formed penetrating through the cryostat and passing through the center of said split gap in the vertical direction, and a sample to be measured and an NMR probe having a solenoid-type probe coil are inserted in said second room-temperature space. Further, the NMR analyzer has a new function constituted by a system for irradiating and detecting the electromagnetic waves having wavelengths of shorter than 0.1 mm.

This application is a continuation of U.S. patent application Ser. No.10/315,215, filed Dec. 10, 2002 now U.S. Pat. No. 6,859,036, the entiredisclosure of which is hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an NMR analyzer.

2. Description of the Related Art

The NMR analyzer is an apparatus for evaluating and analyzing physicaland chemical properties of a sample by placing the sample to be measured(to-be-measured sample) in a space of homogeneous static magnetic field,irradiating the to-be-measured sample with electromagnetic waves, and byutilizing the phenomenon of nuclear magnetic resonance that occurs.

A basic constitution of the NMR analyzer has been closely disclosed in a“Book of NMR”, Yoji Arata, Maruzen Co., 2000. In general, the NMRanalyzer is constituted by at least a superconducting magnet forgenerating a static magnetic field, a probe for emitting electromagneticwaves onto a sample and for receiving freely induced decay signalsemitted from the sample, a high-frequency power source for feeding ahigh-frequency current to the probe, an amplifier for amplifying freelyinduced decay signals, a detector for detecting signals, and an analyzerfor analyzing the signals detected by the detector. The probe is chieflya saddle-type or a cage-type probe coil, and usually has a function forirradiating the sample with electromagnetic waves and a function forreceiving signals emitted from the sample. Further, a multi-layerair-core solenoid is used as the superconducting magnet to generate amagnetic field in the vertical direction. The superconducting magnetmust be cooled with liquid helium and is, hence, contained in alow-temperature container called cryostat. The to-be-measured sample isinserted from the upper side of the room-temperature space penetratingthrough the cryostat up and down, and the probe is inserted from thelower side thereof.

At present, a method of analyzing organic matters by utilizing thenuclear magnetic resonance has been rapidly developing. Concretelyspeaking, organic compounds such as proteins having complex molecularstructures can be efficiently analyzed for their structures on an atomiclevel by setting the resonance frequency of protons to be not lower than500 MHz and by establishing a central magnetic field of not smaller than11.5 T by using strong superconducting magnets. In this case, a highlyhomogeneous magnetic field of not larger than 0.1 ppm is required at asample position near the center. As a practical product, an apparatus of900 MHz having a magnetic field intensity of 21.1 T has been placed inthe market, and still efforts have been made to develop an apparatus of1 GHz having a magnetic field intensity of 23.5 T.

The NMR analyzer must measure the proteins having complex molecularstructures maintaining good sensitivity, and has so far been developedby simply increasing the intensity of magnetic field in which the sampleis placed without changing the fundamental constitution of theapparatus.

However, an increase in the sensitivity is accompanied by an increase inthe size of the apparatus. For example, the superconducting magnetbecomes higher than 5 m and heavier than 5 tons. The bulkysuperconducting magnet generates leaking magnetic field of as long as 10m and must be installed in a dedicated building. Besides, theto-be-measured sample and the probe must be loaded at the center of themagnetic field. With the bulky apparatus, however, this operationbecomes a burden. For example, the probe is inserted from the lower sideof the cryostat and, hence, a space of as wide as 2 m is necessary forthe insertion. This further makes it necessary to place the cryostat ona rack causing the center of gravity of the apparatus to become high andmaking it difficult to suppress its own vibration to a sufficientdegree. Further, an enhanced ability of the superconducting wiresnecessitates the cooling with superconducting helium and, hence,requires cumbersome maintenance and an increased cost for themaintenance.

As for the effect for improving the sensitivity relying upon the shapeof the probe coil, it has heretofore been known that the sensitivity canbe improved by about 1.5 to about 3 times if a solenoid coil is used asthe probe coil bringing about various advantages as compared to those ofthe saddle type or the cage type as disclosed in the above “Book of NMR”For example, advantage is obtained concerning easy control of impedance,filling factor and efficiency of RF magnetic field. With thesuperconducting magnet that generates electric field in the verticaldirection, however, the high-frequency pulse magnetic field must beemitted to the sample in the horizontal direction. Therefore, it ispractically difficult to wind the solenoid coil around the sample tubewhich is filled with a proteinaceous aqueous solution and is oriented inthe vertical direction. Therefore, this superconducting magnet has notbeen generally used.

SUMMARY OF THE INVENTION

It is therefore an object of the invention to provide a high-resolutionNMR analyzer which can be favorably installed, excellently operated andis compact in size.

In order to solve the above object of the invention, the inventionemploys the following measures.

A first measure is concerned with an NMR analyzer comprising asplit-type multi-layer cylindrical superconducting coil systemhorizontally arranged in a cryostat, a first space formed penetratingthrough the split-type multi-layer cylindrical superconducting coilsystem, and a second space formed in the split gap.

A second measure is concerned with the first measure, wherein a ratio ofthe maximum empirical magnetic field to the central magnetic field isnot larger than 1.3.

A third measure is concerned with the first measure, further having ashim coil arranged in the second space.

A fourth measure is concerned with an NMR analyzer comprising asplit-type multi-layer cylindrical superconducting coil systemhorizontally arranged in a cryostat, a first space formed penetratingthrough the split-type multi-layer cylindrical superconducting coilsystem, a second space formed in the split gap, and a third spaceintersecting the second space.

A fifth measure is concerned with an NMR analyzer wherein a firstroom-temperature space is formed penetrating through a cryostat along acenter axis of a split-type multi-layer cylindrical superconducting coilsystem which has a ratio of the maximum empirical magnetic field to thecentral magnetic filed of not larger than 1.3 and is horizontallyarranged such that the center axis of the coil is in the horizontaldirection, a room-temperature shim coil system is arranged in the firstroom-temperature space to improve the homogeneity of the magnetic field,a second room-temperature space is formed penetrating through thecryostat and passing through the center of the split gap in the verticaldirection, and a sample to be measured and an NMR probe having asolenoid-type probe coil are inserted in the second room-temperaturespace. This makes it possible to provide an NMR analyzer which featureshigh sensitivity, high precision and which can be favorably installed.

A sixth measure is concerned with an NMR analyzer wherein a firstroom-temperature space is formed penetrating through a cryostat along acenter axis of a split-type multi-layer cylindrical superconducting coilsystem which has a ratio of the maximum empirical magnetic field to thecentral magnetic filed of not larger than 1.3 and is horizontallyarranged such that the center axis of the coil is in the horizontaldirection, a room-temperature shim coil system is arranged in the firstroom-temperature space to improve the homogeneity of the magnetic field,a second room-temperature space is formed penetrating through thecryostat and passing through the center of the split gap in the verticaldirection, a sample to be measured is inserted in the secondroom-temperature space, a third room-temperature space is formedpenetrating through the cryostat and intersecting the firstroom-temperature space at right angles thereto, and an NMR probe havinga solenoid-type probe coil is arranged in the space.

A seventh measure is concerned with an NMR analyzer wehrein a firstroom-temperature space is formed penetrating through a cryostat along acenter axis of a split-type multi-layer cylindrical superconducting coilsystem which has a ratio of the maximum empirical magnetic field to thecentral magnetic filed of not larger than 1.3 and is horizontallyarranged such that the center axis of the coil is in the horizontaldirection, a room-temperature shim coil system is arranged in the firstroom-temperature space to improve the homogeneity of the magnetic field,a second room-temperature space is formed penetrating through thecryostat and passing through the center of the split gap in the verticaldirection, and a sample to be measured and an NMR probe having asolenoid-type probe coil are inserted in the second room-temperaturespace, wherein the first room-temperature space is further provided witha system for irradiating electromagnetic waves of wavelengths of notloner than 0.1 mm.

An eighth measure is concerned with an NMR analyzer wherein a firstroom-temperature space is formed penetrating through a cryostat along acenter axis of a split-type multi-layer cylindrical superconducting coilsystem which has a ratio of the maximum empirical magnetic field to thecentral magnetic filed of not larger than 1.3 and is horizontallyarranged such that the center axis of the coil is in the horizontaldirection, a room-temperature shim coil system is arranged in the firstroom-temperature space to improve the homogeneity of the magnetic field,a second room-temperature space is formed penetrating through thecryostat and passing through the center of the split gap in the verticaldirection, a sample to be measured and an NMR probe having asolenoid-type probe coil are inserted in the second room-temperaturespace, and a third room-temperature space is formed penetrating throughthe cryostat and intersecting the first room-temperature space at rightangles thereto.

A ninth measure is concerned with the fifth to eighth measures, whereinthe third room-temperature space is provided with a system forirradiating electromagnetic waves having wavelengths of not larger than0.1 mm, or with a system for irradiating electromagnetic waves havingwavelengths of not larger than 0.1 mm and with an electromagnetic wavedetection system.

A tenth measure is concerned with the fifth to ninth measures, whereinthe magnetic field at the center of the coil is not smaller than 11.5 T.

An eleventh measure is concerned with the first to tenth measures,wherein the total height of the apparatus is not larger than 2.0 m.

A twelfth measure is concerned with the seventh or ninth measure,wherein the electromagnetic waves are any one kind of, or a plurality ofkinds of, far infrared rays, infrared rays, visible rays, ultravioletrays, X-rays and γ-rays.

A thirteenth measure is concerned with the fifth to twelfth measures,wherein the distance along the center axis is not larger than 1.5 mbetween the floor surface and the split-type multi-layer cylindricalsuperconducting coil system horizontally arranged in a manner that thecenter axis of the coil thereof is in the horizontal direction.

In order to generate a horizontal magnetic field, the invention uses thesplit-type multi-layer cylindrical superconducting magnet that ishorizontally arranged. To generate an intense magnetic field, the coilis formed in a multiplicity of layers, the outer layers being formed bywinding an NbTi wire and the inner layers being formed by winding anNb₃Sn wire having excellent intense magnetic field characteristics.Usually, several kinds of wires are used depending upon the magneticfield characteristics. Since the cylindrical coil having an axial lengthgreater than the diameter thereof is horizontally arranged, the heightof the apparatus can be suppressed to be not larger than one-halfcompared to the height of the apparatus which is vertically arranged.The split-type is employed in order to insert the sample and the probein the center of the magnetic field. Here, if the split gap is great,the magnetic field is generated at a decreased efficiency at the center,and a maximum empirical magnetic field of the superconducting coilincreases. In the invention, the ratio of the maximum empirical magneticfield and the central magnetic field in this case is desirably set to benot larger than 1.3. In the split coil, a tremendously largeelectromagnetic force acts among the coils in the direction ofcompression. Therefore, the split gap must be of a structure thatwithstands the electromagnetic force, and forming a too large space isnot desirable.

The superconducting magnet in the NMR analyzer must have a magneticfield homogeneity of as high as 0.1 ppm or smaller in the sample spaceof a diameter of 10 to 20 mm. Therefore, a superconducting shim coilsystem is arranged on the outer peripheral side together with thearrangement of the combined coil. Further, the time stability must be ashigh as 0.01 ppm/h or smaller. Therefore, the coils are constituting aso-called permanent current coil in which superconducting wires areconnected to each other in a superconducting manner.

The NMR probe uses a solenoid-type probe coil which, in the invention,can be inserted from the lower side of the room-temperature space thatis penetrating through up and down. Since the apparatus is horizontallyarranged, the distance from the lower end of the cryostat to the centerof the magnetic field is suppressed to be not larger than 1 m,facilitating the insertion. Besides, no particular attention needs bepaid to the distance between the lower end of the cryostat and thesurface of the floor. In the invention, further, the room-temperaturespace may be constituted from the side of the cryostat, and the probemay be inserted from the horizontal direction. Here, no space for accessis required between the lower end of the cryostat and the floor surface,and the height of the apparatus can be further decreased. Even wheninserted in the horizontal direction, the solenoid-type probe coil has asolenoid axis which is at right angles with the direction of themagnetic field.

The NMR analyzer of the invention has a decreased height facilitatingthe operation for replacing the samples.

Another feature of the horizontally arranged type is that the height ofthe ceiling of the building can be suppressed to be from about 2.5 toabout 3 m. Since the center of gravity exists at a low position, acountermeasure can be easily taken against oscillation due toearthquake. It can therefore be the that the NMR analyzer can befavorably installed.

In the invention, further, a plurality of access ports can be easilyprovided. Therefore, the NMR analyzer is not limited to the traditionalfunctions only but offers a multiplicity of functions in the study ofmutual action among the proteins and chemical reactions, enabling thesamples to be easily irradiated with electromagnetic waves such as lightand X-rays.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a sectional view illustrating the basic constitution of an MNRanalyzer according to Embodiment 1 of the invention.

FIG. 2 is a view showing the appearance of the NMR analyzer according toEmbodiment 2 of the invention.

FIG. 3 is a sectional view illustrating the basic constitution of theNMR analyzer according to Embodiment 3 of the invention.

FIG. 4 is a sectional view illustrating the basic constitution of theNMR analyzer according to Embodiment 4 of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiment 1

FIG. 1 is a sectional view illustrating the constitution of an NMRanalyzer according to Embodiment 1 The NMR analyzer of this Embodiment 1includes a cryostat 3 which comprises a liquid helium vessel 7, aheat-shielding plate 10, a vacuum vessel 9 and a liquid helium reservoirprovided at an upper portion; and a split-type multi-layer cylindricalsuperconducting coil system 1 horizontally arranged in the cryostat. Thecryostat 3 itself is installed on an oscillation-proof rack, and thesplit-type cylindrical superconducting coil system 1 is secured in thecryostat 3 by using a load support that permits the infiltration oflittle heat. The cryostat without the liquid helium reservoir has anouter diameter of about 1000 mm and a length of about 1200 mm. Theliquid helium reservoir has a height of 500 mm. Under the cryostat, aspace of about 800 mm is provided for inserting the NMR probe.Therefore, the overall height of the cryostat from the surface of thefloor is 2500 mm. The split-type multi-layer cylindrical superconductingcoil system 1 has an inner diameter of 70 mm, an outer diameter of 600mm, and the axial length thereof is 1000 mm inclusive of asuperconducting connection portion at the end of the coil. Thesplit-type cylindrical superconducting coil system 1 weighs about 0.9tons, and the total weight of the NMR analyzer inclusive of theoscillation-proof rack is about 1.8 tons. The magnetic field that isgenerated is 14.1 T at the center, and a maximum empirical magneticfield is 17.2 T.

The split-type multi-layer cylindrical superconducting coil system 1 hasan outer layer of an NbTi wire, an intermediate layer of a highlywithstanding Nb₃Sn wire and an inner layer of a high-magnetic-fieldNb₃Sn wire, which are wound in the form of coils. Though FIG. 1 showsthree layers in a simplified manner, each of them is further dividedinto two layers. Therefore, there is constituted a multi-layer coil of atotal of six layers. The split gap is 100 mm.

A superconducting shim coil system 2 is arranged on the outer side ofthe superconducting coil system 1 and is entirely immersed in liquidhelium 8.

A first room-temperature space 4 is formed penetrating through thecryostat 3 along the center axis of the split-type multi-layercylindrical superconducting coil system 1. The first room-temperaturespace 4 has a room-temperature space diameter of 50 mm, employs a vacuumadiabatic structure, and is secured by welding to the cryostat 3. In thefirst room-temperature space 4 is further arranged a room-temperatureshim coil system 6 for improving the homogeneity in the magnetic field.

In a direction (up-and-down direction on the surface of the paper inFIG. 1) perpendicular to the center axis, further, a secondroom-temperature space 5 is formed penetrating through the cryostat 3passing the center of split gap of the split-type multi-layercylindrical superconducting coil system 1. The second room-temperaturespace 5 has a room-temperature space diameter of 50 mm, and is arrangednearly at the center of the cryostat 3 in the direction of length so asto be vertically oriented up and down.

The first room-temperature space 4 and the second room-temperature space5 are intersecting at a central position of the superconducting coilsystem 1, and are welded to each other to maintain vacuum adiabaticperformance. A to-be-measured sample is arranged in the intersectingspace. For example, the to-be-measured sample 11 and an NMR probe 12having a solenoid-type probe coil are inserted in the space where thefirst room-temperature space 4 and the second room-temperature space 5of FIG. 1 intersect each other. Here, the room-temperature shim coilsystem 6 inserted and arranged in the first room-temperature space hasbeen specially contrived to maintain the homogeneity of magnetic fieldin the central region of the magnetic field to where the sample is set.Namely, in this application which uses the split-type superconductingcoil and in which the second room-temperature space 5 is intersectingthereto at right angles, the coil wiring at the center of theroom-temperature shim coil system 6 is so contrived as will not tointerrupt the insertion of the NMR probe 12 from the lower side.Further, the NMR probe 12 inserted in the second room-temperature space5 has a solenoid-type probe coil, the center axis of solenoid of theprobe coil being in the vertical direction, i.e., the direction ofmagnetic field thereof being in the horizontal direction, so that thetwo meet at right angles with each other.

The NMR analyzer of this Embodiment 1 has a proton resonance frequencyof 600 MHz. However, use of the probe coil of the type of solenoid coilhelps improve the SN sensitivity by about 1.5 times as compared to theconventional vertical-type 600 MHz apparatus. This means that thesensitivity is equivalent to that of the conventional 900 MHz NMRanalyzer and, besides, the weight and the height of the apparatus areboth decreased to one-half or smaller, accomplishing a compact size.

As described above, the NMR analyzer of the invention offers excellencein the installation and operation.

Embodiment 2

FIG. 2 shows the appearance of the NMR analyzer according to Embodiment2. In this Embodiment 2, the constitution of Embodiment 1 is furtherprovided with a third room-temperature space 15 so as to intersect thefirst room-temperature space 4 and the second room-temperature space 5at right angles. In Embodiment 1, the NMR probe is inserted in thesecond room-temperature space 5 from the lower side. In this Embodiment2, however, the NMR probe can be inserted from the horizontal directionby using the third room-temperature space 15. The NMR probe that is usedis the solenoid-type probe coil, the solenoid axis being verticallyoriented. The to-be-measured sample is inserted in the secondroom-temperature space 5 from the upper side, and the room-temperatureshim system is incorporated in the first room-temperature space 4.

In this Embodiment 2, no access is necessary from the lower side of thesecond room-temperature space 5, and space can be omitted between thecryostat 3 and the oscillation-proof rack enabling the overall height ofthe apparatus to be lowered down to 1700 mm. This makes it possible toimprove the operability of the NMR probe, to improve the operabilitysuch as of replacing the samples, and to facilitate the installationwith respect to the height of the ceiling.

Embodiment 3

FIG. 3 is a sectional view illustrating the constitution of the NMRanalyzer according to Embodiment 3. In this Embodiment 3, the NMRanalyzer fabricated in Embodiment 1 is further provided with a system 13for irradiating electromagnetic waves of wavelengths of smaller than 0.1mm in the first room-temperature pace 4 as a novel function.

There are still many uncertainties concerning the mutual reactions andchemical reactions of proteins, and the study must be conducted in thefuture from a variety of viewpoints. Here, it is important to let theeffects of electromagnetic waves such as light and X-rays be known. Byusing the NMR apparatus of this Embodiment 3, the electromagnetic waveirradiation system can be easily incorporated and used. Theelectromagnetic waves to be used may include far infrared rays ofwavelengths of 0.1 mm or shorter through up to visible light rays,X-rays and γ-rays. Relying upon this constitution, the NMR apparatusaccording to Embodiment 3 enables the first room-temperature space orthe third room-temperature space to be provided with the mechanism forirradiating and detecting electromagnetic waves of wavelengths ofshorter than 0.1 m.

As described above, operability of the NMR probe is improved,operability such as replacing the samples is improved and installationis improved concerning the height of the ceiling. According to the NMRanalyzer of this Embodiment 3, further, access ports can be easilyadded.

Embodiment 4

FIG. 4 is a sectional view illustrating the constitution of the NMRanalyzer according to Embodiment 4. In this Embodiment 4, anelectromagnetic wave detection system 14 is further arranged inEmbodiment 3. In Embodiment 3, the effect of the electromagnetic waveirradiation is measured by the NMR analysis. In this Embodiment 4, onthe other hand, the absorption spectra of electromagnetic waves and theintensities thereof are measured by the electromagnetic detection system14 in parallel with the NMR analysis.

It is meaningful to select a transparent vessel material for the NMRprobe and the sample chamber so that the electromagnetic waves directlyarrive at the sample, and to form a gap in the NMR probe coil tofacilitate the transmission of the electromagnetic waves.

According to the invention as described above, there is provided an NMRanalyzer offering excellence in the installation and operability, andfeaturing compactness and high sensitivity.

1. An NMR analyzer comprising: a split-type multi-layer cylindricalsuperconducting coil system which has a ratio of the maximum empiricalmagnetic field to the central magnetic filed of not larger than 1.3, andwhich is horizontally arranged such that a center axis of the coilsystem is in the horizontal direction, a cryostat housing saidsplit-type multi-layer cylindrical superconducting coil system, a firstroom-temperature space formed penetrating through said cryostat alongsaid center axis, a room-temperature shim coil system is arranged insaid first room-temperature space to improve magnetic field homogeneitytherein, a second room-temperature space formed penetrating through thecryostat and passing through the center of a split gap of saidsplit-type multi-layer cylindrical superconducting coil system in avertical direction, an NMR probe having a solenoid-type probe coilinserted in said second room-temperature space, and an electromagneticwave-irradiating system for irradiating electromagnetic waves ofwavelengths of not larger than 0.1 mm, and which is provided in saidfirst room-temperature space.
 2. An NMR analyzer according to claim 1,further comprising a third room-temperature space is formed penetratingthrough the cryostat and intersecting the first room-temperature spaceand said second room-temperature space at right angles thereto.
 3. TheNMR analyzer according to claim 1, wherein said central magnetic fieldis not smaller than 11.5 T.
 4. The NMR analyzer according to claim 1,wherein the overall height of said NMR analyzer is not larger than 2.0m.
 5. The NMR analyzer according to claim 1, wherein the electromagneticwaves are any one kind of, or a plurality of kinds of, far infraredrays, infrared rays, visible rays, ultraviolet rays, X-rays and γ-rays.6. The NMR analyzer according to claim 1, wherein the distance alongsaid center axis is not larger than 1.5 m between a cryostat installingfloor surface and the split-type multi-layer cylindrical superconductingcoil system.
 7. The NMR analyzer according to claim 1, furthercomprising an electromagnetic wave detection system for detectingelectromagnetic waves having wavelengths of not larger than 0.1 mm.